1. Field of the Invention
Embodiments of the present invention generally relate to the field of the treatment of body lumens, more particularly to the field of the treatment of blood vessels, and more particularly to the treatment of blood vessel aneurysms with stents, lined stents such as stent grafts, and the use of pharmaceutical agents therewith for the treatment of localized blood vessel phenomena, such as aneurysm.
2. Description of the Related Art
Aneurysm, i.e., the enlargement of a blood vessel at a specific location therein to the point where rupture of the blood vessel is imminent, has been treated in the past by surgical intervention techniques, whereby the affected portion of the blood vessel is removed and is replaced by a synthetic graft. This treatment regimen is highly invasive for the patient, and typically requires a multiple day post-operative hospital stay, as well as several months of recovery time until the patient has fully recovered from the surgery. Additionally, some patients may not capable of undergoing such a procedure due to morbidity or other overall health issues.
To address the limitations imposed by surgical intervention to replace the aneurysmal blood vessel region with an artificial graft, a new technique has been developed by which the aneurysmal blood vessel site is treated by placing a lined stent, known in the art as a stent graft, within the blood vessel in a position by which the tubular body of the stent graft spans the interior of the weakened area of the blood vessel wall. The stent graft, properly positioned, will allow blood to flow through the hollow tubular interior thereof, and also prevent blood, under systemic pressure, from reaching the weakened blood vessel wall at the aneurysmal site spanned by the tubular body thereof. However, there is still the opportunity for blood to reach the weakened wall location, such as through leakage of blood between the stent and the vessel wall and thus into the weakened region, diffusion of blood through the stent material itself, or re-supply of blood into the aneurysmal sac from adjacent blood vessels. In each case, there is a renewed risk that the blood vessel may rupture. Furthermore, there remains a risk of additional deterioration of the blood vessel wall at the aneurysmal location even in the absence of blood leakage into the region isolated by the stent graft or the renewed supply of blood to the isolated region.
Typically, surgical intervention for aneurysm repair is not indicated until the blood vessel diameter, at the aneurysmal site, is at least 150 to 300% of its normal diameter. Below this threshold, the normal course of treatment has been to monitor the site, and if the diameter of the blood vessel wall at the aneurysmal site continues to expand beyond an undesirable threshold diameter, intervene surgically. Recently, it has been found that the application of certain antibiotics and other aneurysmal attack inhibitors, can reduce the severity and/or progression of an aneurysm, and thereby reduce the likelihood of the need for surgical intervention to repair the aneurysm. It is postulated that the antibiotic or other inhibitor reduces the level of an elastin or collagen attacking protein in the bloodstream and blood vessel wall, specifically matrix metalloproteinasis, MMP2 and MMP9. This reduces the severity of an attack based on MMP2 and MMP9 and other MMPs on the elastin cells in the blood vessel wall and thus reduces the severity and the progression of the aneurysm. Antibiotics such as doxycycline, as well as beta adregenic blockage agents, ACE inhibitors, anti-inflammation drugs have been found to suppress aneurysm progression.
Typical antibiotic or other based treatment requires the use of systemic antibiotics, either orally, intramuscularly or intravenously introduced, in a dosage sufficient to ensure that the quantity of antibiotic reaching the aneurysm is sufficient to affect the elastin, collagen attacking protein level at the aneurysm site. Thus, far more antibiotic must be used than that needed to treat the aneurysm, because a substantial portion of the antibiotic is directed to locations other than the aneurysmal site. The systemic use of antibiotics to treat localized sites can lead to serious side effects, including the occurrence of drug resistant bacteria, gastrointestinal disruption, and the like. The longer the duration of time that antibiotics are taken, and the higher the dosage, the higher the risk of such serious side effects.
One additional proposed mechanism for treating blood vessels which are in an aneurysmal state, but for which surgery is not yet indicated, is to introduce “micro-spheres” containing a quantity of a therapeutic agent, into the sac space between the sac wall and the stent graft. Such microspheres are constructed to provide a time release of the pharmaceutical agent, and thus provide long term dosing of the aneurysmal site. These microspheres are typically configured to have a diameter on the order of 50 microns or more, such that sufficient therapeutic agent can be carried therein to enable a relatively long-term release of the therapeutic agent from the microsphere into the bloodstream. Because, microspheres of this size can cause substantial complications, such as the blockage of smaller capillaries or distal thrombosis; they are not recommended to be introduced in the blood stream. Additionally, only a small portion of the therapeutic agent released from the microspheres actually reaches the aneurysm, because the majority of the agent becomes distributed throughout the body by the patient's blood. Therefore, although the microspheres provide the patient with longer term regular dosing of the therapeutic agent, and thus free the patient from the need to regularly ingest or inject the agent, they do not provide long term localized delivery of therapeutic agents directly to the aneurismal site.
Therefore, there exists a need in the art for a localized drug delivery system, which will allow timed delivery of therapeutic agents to an aneurysmal site in a blood vessel, after placement of a bypassing element or prosthesis, such as placing a stent graft in the blood vessel to span the aneurysmal site, without the need for systemic application of the therapeutic agent.